Despite the ubiquitous use of metal complexes in organic reactions, a simple process for their removal has yet to be discovered. Unfortunately, residual metals often must be removed from the reaction mixture because they can interfere with subsequent transformations and can pose problems for shelf-life and use of the final product.
Current process for removing metal complexes involve running the reactant mixture through numerous columns or other similarly rigorous purification strategies. In addition to being cumbersome, these procedures are time consuming and labour intensive. As uses for metal complexes increases, a simple and facile process for their removal is increasingly needed and desired.
U.S. Pat. No. 6,376,690 discloses a process of removing residual metals from a solution by adding a solubility-enhancing compound, where through the relative solubilities between two solutions are manipulated so as to cause the metal complex in a first solution to transfer into a second solution that is generally immiscible with the first solution. The removal of the second solution thus also removes the metal complex from the reaction mixture.
U.S. Pat. No. 6,376,690 recommend phosphines as useful solubility-enhancing compounds. However, the examples disclosed in this invention, only demonstrate that the use of a special water-soluble phosphine, i.e. trishydroxymethylphosphine (THP) in combination with triethylamine, is able to reduce the Ruthenium content of different simple ether and ester products. With respect to the large scale synthesis of more highly functionalized organic compounds, treatments with THP solutions may cause undesired side reactions. These side reactions may be due to formaldehyde present in THP solutions, which are most easily accessible for large scale operations by means of alkaline deformylation of commercially available aqueous tetrakis(hydroxymethyl)phosphonium salts (TKC).
Moreover, in view of a potential commercial use on large scale, phosphines generally exhibit the disadvantage of being very susceptible towards oxidation. This implies that special measures have to be taken to protect these air sensitive and/or pyrogenic compounds from contact to oxygen and, hence, guarantee their desired efficiency. Hence, these phosphoric compounds are released in situ in separate vessels under inert conditions, increasing the complexity of the large scale processes. In addition, phosphines are toxic and therefore not useful in food or pharmaceutical industry, since any product contamination by these compounds has to be strictly avoided.
Surprisingly it was found, that these pitfalls can be avoided by the use of compounds of formula A
wherein,    Ra is SH, SO3H, OH or COOH;    Rb is SH, OH or COOH;    Rc each independently is H, SH, OH or COOH;    Rd each independently is H or COOH;    n is 1, 2, 3, 4 or 5;or a salt or an activated form thereof.